DNA damage can persist for years, increasing cancer risks

Ever since scientists discovered DNA’s crucial role in life, they’ve known our cells have built-in repair systems to fix damaged genetic material. But recent research has revealed something unexpected – some types of DNA damage can dodge these repair mechanisms and lurk in our cells for years, creating multiple opportunities for cancer-causing mutations.

The research team, led by Dr. Michael Spencer Chapman from the Wellcome Sanger Institute and the Barts Cancer Institute, made this discovery by studying an impressive collection of cellular family trees.

The findings, published in the journal Nature, challenge long-held beliefs about how DNA damage works.

Some DNA damage lingers for years

The scientists analyzed family trees of hundreds of single cells from individuals. These trees, pieced together from shared mutation patterns, provide insights into the ancestry of cells.

By examining blood stem cells, bronchial epithelial cells, and liver cells, researchers uncovered unexpected patterns of mutation inheritance.

In blood stem cells, up to 20% of mutations arise from specific DNA damage that remains unrepaired for two to three years or longer.

“With these family trees, we can link the relationships of hundreds of cells… meaning we can track back through the divisions each cell has gone through,” explained Dr. Chapman.

This persistence means damaged DNA can repeatedly introduce mutations during cell division. Each attempt to replicate the damaged DNA risks generating new errors, creating multiple chances for cancer-causing mutations.

DNA mutations and structural alterations

DNA damage and mutations are related but distinct concepts. A mutation occurs when one of the DNA bases (A, T, C, or G), which are the “letters” of the genetic code, is in the wrong position.

This is similar to a typo in a written sentence. For example, replacing a “C” with a “T” changes the meaning of the genetic instruction.

DNA damage, on the other hand, refers to chemical alterations to the DNA’s structure itself. Instead of a “wrong letter,” it’s like a letter being smudged or distorted, making it unreadable. This type of damage can prevent the DNA from being properly copied or understood.

DNA damage and cancer risk

If the cell’s repair mechanisms fail to fix the damage, it can create permanent mutations during cell division.

When the cell replicates its DNA, it may misinterpret or incorrectly copy the damaged section, introducing errors into the genetic code. These errors can accumulate and, over time, contribute to diseases like cancer.

“When exploring family trees of blood stem cells, we found a type of DNA damage that results in around 15 to 20 percent of the mutations and can last for several years,” noted study co-author Emily Mitchell.

This finding raises critical questions: Why does this persistent damage occur in blood stem cells but not other tissues? What is the exact nature of this damage?

Implications for cancer research

Persistent DNA damage presents a challenge to what scientists previously believed about how cancer mutations form. Until now, the assumption was that most DNA damage is either repaired quickly or eliminated, preventing long-term effects.

However, this study reveals that some types of DNA damage can persist for years without repair, causing mutations each time cells divide. These findings reshape our understanding of how mutations accumulate over time and their role in diseases like cancer.

“These findings don’t fit with what scientists have previously thought. This paradigm shift brings a new dimension to the way we think about mutations,” noted co-author Dr. Peter Campbell.

Understanding why some DNA damage escapes repair and persists for years offers new avenues for cancer prevention and treatment. Intervening to repair or eliminate such damage could significantly reduce mutation rates.

The research also highlights the importance of curiosity in science. “This study is a prime example of exploratory science – you don’t always know what you’re going to find until you look,” Dr. Chapman noted.

Targeting DNA damage to combat cancer

This study from Wellcome Sanger Institute and Barts Cancer Institute changes our understanding of how DNA damage contributes to cancer. Previously, scientists believed most DNA damage was quickly repaired by the body’s natural mechanisms.

However, the research shows that certain types of damage can persist for years without being fixed. These long-lasting forms of damage can repeatedly introduce mutations every time cells divide, increasing the risk of harmful changes that lead to cancer.

By uncovering this process, scientists have created new opportunities to study and combat cancer. For example, understanding why some DNA damage evades repair may lead to treatments that target and fix these persistent issues, reducing mutation rates and preventing cancer development.

As we learn more about our genome – the complete set of DNA in our bodies – this study highlights how even tiny, hard-to-detect changes in DNA can have significant impacts on our health. It serves as a reminder that understanding these small changes is key to tackling major diseases like cancer.

The study is published in the journal Nature.

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